Tolvaptan, 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl amino)benzoyl]-2,3,4,5,-tetrohydro-1H-benzoazepine represented by the following general formula is used as a vasopressin antagonist.

The U.S. Food and Drug Administration has approved the new drug application of tolvaptan (vasopressin receptor 2 antagonist) manufactured by Otsuka Pharmaceutical Co. In a heart failure model, tolvaptan only exhibited hydragogue diuresis effected and decreased heart preload significantly, while having no effect on heart afterload and renal failure. Many clinical trials for treating heart failure and hyponatremia have proven that tolvaptan can decrease fluid retention and increase the serum sodium concentration. Tolvaptan can also relieve the symptom of pulmonary congestion, cause weight loss, protect the kidney function and has no severe adverse effects. It has been proven that tolvaptan is specifically useful in the treatment of clinically significant hypervolemic and normovolemic hyponatremia associated with congestive heart failure, cirrhosis and the syndrome of inappropriate antidiuretic hormone (SIADH).
Tolvaptan, white crystal or crystalline powder, is only slightly soluble in water. Therefore it is inevitable for tolvaptan to have a low bioavailability when administered orally.
In order to solve this problem, Japanese Patent No. JP 11021241 A disclosed a preparation method of a solid tolvaptan composition comprising the following steps: tolvaptan and hydroxypropyl cellulose are dissolved in an organic solvent at a certain ratio, the organic solvent is removed via spray dry method to obtain tolvaptan solid dispersion composition, and other pharmaceutically acceptable excipients are added to obtain the final solid preparation.